Delineation of Brain Tumor Extent with [C]L-Methionine Positron Emission Tomography: Local Comparison with Stereotactic Histopathology

Purpose: Methyl-[C]L-methionine ([C]MET) positron emission tomography (PET) in brain tumors reflects amino acid transport and has been shown to be more sensitive than magnetic resonance imaging in stereotactic biopsy planning. It remains unclear whether the increased [C]MET uptake is limited to solid tumor tissue or even detects infiltrating tumor parts. Experimental Design: In 30 patients, a primary or recurrent brain tumor was suspected on magnetic resonance imaging. Patients were investigated with [C]MET-PET before stereotactic biopsy. The biopsy trajectories were plotted into the [C]MET-PET images with a newly designed C-based software program. The exact local [C]MET uptake was determined within rectangular regions of interest of 4 mm in width and length aligned with the biopsy specimen. Individual histologic specimens were rated for the presence of solid tumor tissue, infiltration area, and nontumorous tissue changes. Results: Receiver operating characteristics analysis demonstrated a sensitivity of 87% and specificity of 89% for the detection of tumor tissue at a threshold of 1.3-fold [C]MET uptake relative to normal brain tissue. At this threshold, only 13 of 100 tumor positive specimen were false negative mainly in grade 2 astrocytoma. In grade 2 astrocytoma, mean [C]MET uptake in the infiltration area was significantly higher than in solid tumor tissue (P < 0.003). Conclusions: [C]MET-PET detects solid parts of brain tumors, as well as the infiltration area at high sensitivity and specificity. High [C]MET uptake in infiltrating tumor of astrocytoma WHO grade 2 reflects high activity in this tumor compartment. Molecular imaging, with [C]MET, will guide improved management of patients with brain tumors.